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Results for “Lithium Chloride”

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PubMed2000

Chronic lithium chloride injection increases glucocorticoid receptor but not mineralocorticoid receptor mRNA expression in rat brain.

Lithium has been used clinically for the treatment of bipolar disorders. However, the brain mechanisms, by which lithium acts, are still unclear. An impaired hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathogenesis of mood disorders. In this study, we investigated the effects of chronic lithium on the corticosteroid receptors in the brain. Male Wistar rats were injected with LiCl (1.5 mEq/kg) or saline intraperitoneally (i.p.) once a day for 14 days. Twenty-four hours after the last injection, the expressions of mRNA for glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in the brain were determined by non-radioactive in situ hybridization. Chronic administration of LiCl increased the expression of GR mRNA in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). However, no significant changes were observed in the expression of either MR mRNA in the hippocampus or GR mRNA in the locus ceruleus. Since the hippocampus and PVN mediate negative feedback regulation of the HPA axis, an increased expression of GR mRNA in these regions may normalize HPA axis activity in mood disorders. Thus, the effect of chronic lithium on GR function may be involved in its antimanic and/or prophylactic activity in bipolar disorders.

Animals↗
PubMed2001

Inhibition of 20 S and 26 S proteasome activity by lithium chloride: impact on the differentiation of leukemia cells by all-trans retinoic acid.

Lithium affects several enzymatic activities, however, the molecular mechanisms of lithium actions are not fully understood. We previously showed that LiCl interacts synergistically with all-trans-retinoic acid to promote terminal differentiation of WEHI-3B D(+) cells, a phenomenon accompanied by the recovery of the retinoid-induced loss of retinoic acid receptor alpha protein pools. Here, we demonstrate the effects of LiCl on proteasome-dependent degradation of retinoic acid receptor alpha proteins. LiCl alone, or in combination with all-trans-retinoic acid, increased cellular levels of ubiquitinated retinoic acid receptor alpha and markedly reduced chymotryptic-like activity of WEHI-3B D(+) 20 S and 26 S proteasome enzymes. Neither KCl nor all-trans-retinoic acid affected enzyme activity, whereas NaCl produced a modest reduction at relatively high concentrations. In addition, LiCl inhibited 20 S proteasome chymotryptic-like activity from rabbits but had no effect on tryptic-like activity of the 26 S proteasome. This effect has significant consequences in stabilizing the retinoic acid receptor alpha protein levels that are necessary to promote continued differentiation of leukemia cells in response to all-trans-retinoic acid. In support of this concept, combination of proteasome inhibitors beta-clastolactacystin or benzyloxycarbonyl-Leu-Leu-Phe with all-trans-retinoic acid increased differentiation of WEHI-3B D(+) cells in a manner that was analogous to the combination of LiCl and all-trans-retinoic acid.

Adjuvants, Immunologic↗
PubMed1986

Acute and chronic effects of lithium chloride on GABA-ergic function in the rat corpus striatum and frontal cerebral cortex.

The acute (1 h, i.p.) and chronic (14 days, p.o.) effects of LiCl treatment upon GABA-ergic neurons were studied in the rat corpus striatum and frontal cerebral cortex. One hour after a single injection of LiCl the activity of glutamic acid decarboxylase (GAD) was reduced by 29% in the striatum (2 meq/kg LiCl) and by 38% in the cerebral cortex (10 meq/kg LiCl). In contrast, striatal GAD was activated by 34% 1 h after the injection of 10 meq/kg of LiCl; this dose also reduced the endogenous striatal GABA level by 24%. After 14 days of oral LiCl administration (2 meq/kg/day): a) cortical GAD activity was enhanced by 50% and GABA concentration was decreased by 28%; b) no changes were observed in the striatum. These findings suggest that: LiCl administration stimulates GABA-ergic function in specific areas (depending on the dose and length of treatment) increasing both GAD activity and probably GABA release. This occurs in the striatum after acute treatment only with a high dose, and in the frontal cerebral cortex after chronic treatment with a low dose.

4-Aminobutyrate Transaminase↗
PubMed1992

Area postrema mediation of physiological and behavioral effects of lithium chloride in the rat.

The area postrema (AP), a chemoreceptor trigger zone for nausea and vomiting, has been implicated in taste aversion conditioning with LiCl. In addition to taste aversion acquisition, the present studies indicate that a number of other responses to LiCl administration are eliminated by lesions of the AP. These include a behavioral response, 'lying-on-belly' as well as two physiological responses, delayed stomach emptying and hypothermia. These findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin. They also provide strong evidence that the failure to acquire conditioned taste aversions to LiCl-paired flavors after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.

Animals↗
PubMed1987

The anti-proliferative effect of lithium chloride on melanoma cells and its reversion by myo-inositol.

The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with LiCl delayed the appearance of melanoma tumours in syngeneic mice. Growth inhibition of cells was accompanied by morphological and biochemical alterations. LiCl induced cell enlargement and formation of dendrite-like structures. The activity of NADPH cytochrome c reductase, an enzymatic marker of endoplasmic reticulum was significantly (2-3 fold) increased. Addition of myo-inositol to cell cultures partially reversed the anti-proliferative and morphological effects of LiCl on melanoma cells. This finding may suggest that the anti-proliferative effect of LiCl is related to its effect on phosphatidylinositol metabolism.

Animals↗
PubMed1983

[Ultrastructure of Salmonella typhimurium forms with unbalanced growth induced by lithium chloride].

The action of 1.0 and 1.5 M LiCl on S. typhimurium induces the appearance of unbalanced growth forms capable of growing and multiplication, when subcultured in a medium with this preparation. In this culture the prevalence of cells differing in their structure from the initial Salmonella cells and from stable L-form cultures is observed. Cells characteristic of the initial culture and cells resembling the L-forms occur in lesser numbers. LiCl seems to affect peptidoglycan and the cytoplasmic membrane, which brings about disturbances in the permeability of the surface structures of the cell.

Chlorides↗
PubMed1994

Effects of lithium chloride on rabbit blastocyst expansion, and accumulation of phosphoinositides and inositol phosphates.

The effects of lithium, an inhibitor of the recycling of inositol in the phosphatidylinositol cycle, on rabbit blastocyst growth and metabolism of phosphoinositides were investigated. Day 2 rabbit morulae were first cultured for 2 days in basic culture medium and then transferred to medium containing myo-[2-3H]inositol for culture for a further 3 days. At the end of culture, the resulting blastocysts were incubated with LiCl (0, 1, 5, 10, 20 mmol l-1) for 1 h. The blastocysts were then lysed and both the aqueous and lipid portions were analysed for incorporated radioactivity. Thin layer chromatographic separation of the lipid portion indicated that lithium had no significant effect on formation of radiolabelled phosphoinositides. However, high performance anion exchange chromatography indicated that lithium significantly stimulated accumulation of radiolabelled inositol monophosphate and inositol 1,4,5-trisphosphate. This result indicates that the phosphatidylinositol cycle is turning over in rabbit blastocysts. Continuous culture of rabbit embryos for 5 days in media containing LiCl (5, 10, 15 and 20 mmol l-1) significantly decreased blastocyst growth as measured by blastocyst expansion and incorporation of [3H]thymidine. However, supplementing the medium with excess inositol (up to 9375 mumol l-1), in an attempt to increase the intracellular uptake of inositol and thus compensate for the inhibitory effect of lithium on inositol recycling, did not reverse the inhibitory effect of lithium on blastocyst growth.

Animals↗
PubMed1990

Direct effects of lithium chloride on testicular delta 5-3 beta and 17 beta-hydroxysteroid dehydrogenase activities in the rat--in vitro study.

Testicular delta 5-3 beta- and 17 beta-hydroxysteroid dehydrogenase (delta 5-3 beta- and 17 beta-HSD) activities of rat are inhibited in vitro by a wide range of lithium concentration. The inhibitory effects of lithium are evident at a concentration of 2.5 mM which is easily achieved during the treatment of acute manic patients with lithium. This suggests that lithium exerts a direct inhibitory effect on testicular hydroxysteroid dehydrogenase activities.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Chronic lithium chloride fails to prevent imipramine-induced sensitization to the dopamine D(2)-like receptor agonist quinpirole.

Lithium salts, an effective antimanic treatment, are able to prevent the development of the dopaminergic behavioural supersensitivity induced by chronic treatment with neuroleptics, by denervation of the dopaminergic terminal fields and by rapid eye movements (REM) sleep deprivation, which is considered a model of mania. We have studied the effect of a lithium (LiCl) diet, inducing a lithium serum level in the range of therapeutic efficacy, on the development of the supersensitivity to the locomotor effect of the dopamine D(2)-like receptor agonist, quinpirole, induced by chronic treatment with the antidepressant drug, imipramine. The results show that lithium is not able to prevent the development of such behavioural supersensitivity. The present data suggest that antidepressant-induced dopaminergic supersensitivity might provide a useful model of those manic states induced by (or subsequent to) antidepressant treatments. Moreover, the finding is consistent with the view that antidepressant-induced dopaminergic supersensitivity might play a role in the therapeutic effect of these drugs (which is known to be augmented by lithium, and not antagonised). Finally, the results show that the dopaminergic supersensitivity induced by imipramine is qualitatively different from that induced by neuroleptics or denervation of the dopaminergic terminal fields.

Analysis of Variance↗
PubMed1990

Ontogenetic differences in the association of gustatory and tactile cues with lithium chloride and footshock.

Using a double dissociation design with 15% sucrose solution and exposure to a heat lamp (34 degrees C) as CSs and 0.3 M LiCl and 1-mA footshock as USs, the present study found 15-day-old rats to show selective associations similar to those found in adults. Five-day-old pups, however, expressed similar sucrose aversions when this solution was paired with either LiCl or footshock, whereas they expressed heat aversions after heat-LiCl but not heat-shock pairings. Results are discussed with respect to previous data on selective associations in pups, current theories on selective associations, and ontogenetic differences in stimulus selection.

Age Factors↗
PubMedDate not supplied

Effect of lithium chloride on the circadian rhythm in the flight activity of the microchiropteran bat, Taphozous melanopogon.

We have performed experiments on the influence of Li+ offered through drinking water i) on the period length (tau) of the rhythm in the flight of bats under LL and ii) on phase angles during entrainment under LD cycles. Bats subject to entrainment exhibited no qualitative and quantitative change in psi values after Li+ treatment. In contrast the ingestion of Li ions by bats under free-running conditions shortens the tau of the bat rhythm by an amount that is a function of period length prior to ingestion. Tau is, thus homeostatically conserved in the face of Li administration in bats.

Animals↗